Chu Yunchao, Ge Weipeng, Wang Xin
Department of Pain Treatment, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China.
Department of Anesthesiology, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China.
Exp Ther Med. 2019 Dec;18(6):4665-4672. doi: 10.3892/etm.2019.8165. Epub 2019 Nov 4.
MicroRNAs (miRNAs) play crucial roles in the pathogenesis of neuropathic pain. The present study investigated the effects of miR-448 on the progression of neuropathic pain in a rat model of chronic constriction injury (CCI) of the sciatic nerve. Reverse-transcription quantitative polymerase chain reaction was conducted to detect the gene expression. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were used to assess the pain threshold. The protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by ELISA. The target of miR-448 was predicted by TargetScan software. The Student's t-test or one-way ANOVA were used to identify statistical differences among groups. miR-448 was persistently upregulated in CCI rats, and both mechanical allodynia and thermal hyperalgesia in CCI rats were decreased following miR-448 downregulation. The expression levels of IL-1β, IL-6 and TNF-α were significantly increased in CCI rats compared with controls, and these effects were reversed following treatment with a miR-448 inhibitor. A luciferase reporter assay revealed that sirtuin 1 (SIRT1) was a target gene of miR-448. SIRT1 was found to abrogate the effect of miR-448 on neuropathic pain development. Collectively, the results of the present study revealed that miR-448 promoted neuropathic pain in CCI rats by regulating neuroinflammation via SIRT1. Therefore, SIRT1 may be considered as a novel biomarker for neuropathic pain.
微小RNA（miRNA）在神经性疼痛的发病机制中起关键作用。本研究调查了miR-448对坐骨神经慢性压迫损伤（CCI）大鼠模型中神经性疼痛进展的影响。进行逆转录定量聚合酶链反应以检测基因表达。用爪部撤离阈值（PWT）和爪部撤离潜伏期（PWL）评估疼痛阈值。通过酶联免疫吸附测定（ELISA）检测白细胞介素（IL）-6、IL-1β和肿瘤坏死因子-α（TNF-α）的蛋白表达水平。通过TargetScan软件预测miR-448的靶标。采用Student t检验或单因素方差分析确定组间的统计学差异。miR-448在CCI大鼠中持续上调，下调miR-448后，CCI大鼠的机械性异常性疼痛和热痛觉过敏均减轻。与对照组相比，CCI大鼠中IL-1β、IL-6和TNF-α的表达水平显著升高，用miR-448抑制剂处理后这些作用得到逆转。荧光素酶报告基因检测显示，沉默调节蛋白1（SIRT1）是miR-448的靶基因。发现SIRT1可消除miR-448对神经性疼痛发展的影响。总体而言，本研究结果显示，miR-448通过SIRT1调节神经炎症促进CCI大鼠的神经性疼痛。因此，SIRT1可被视为神经性疼痛的一种新型生物标志物。
